Spontaneous Intramural Esophageal Hematoma Secondary to Thrombolysis in the Setting of Pulmonary Embolism

Introduction

Intramural hematoma of the esophagus (IHE) was described for the first time by Williams in 1957. ¹ It is a very uncommon clinical entity, with a prognosis that is essentially benign. ² The most common symptoms are hematemesis, epigastric pain or retrosternal chest pains, odynophagia, and dysphagia. ³ Spontaneous IHE has been reported in the setting of systemic full-dose thrombolytic therapy in the treatment of myocardial infarction, ⁴ pulmonary embolism (PE), ³ and ischemic stroke. ⁵

Catheter-directed thrombolysis (CDT) is an emerging therapeutic option in the treatment of PE, with the intention of decreasing the dosage of the thrombolytic agent via local delivery. ⁶ The mentioned dose reduction is presumed to translate into less bleeding. ⁶ In the present case report, we describe 2 patients with acute PE, complicated by IHE during CDT.

Case Report

Case 1:

The first case was a 79-year-old man, who presented to the emergency department with sudden-onset dyspnea commencing a week before admission and pleuritic chest pains. The patient also mentioned right lower extremity swelling during the previous week and 1 episode of syncope about 6 hours earlier, resulting in loss of posture. He had suffered from hypertension for 30 years and undergone coronary artery bypass graft surgery 20 years earlier. He denied any immobility, recent surgery, or recent travels. He was on aspirin, antihypertensive medications, statins, and sotalol (for 3 years due to frequent premature ventricular contractions). On initial presentation, he had a blood pressure of 86/63 mm Hg, O₂ saturation of 89% in the ambient air, and heart rate of 60 bpm (possibly due to sotalol effect). Electrocardiography showed a normal sinus rhythm, a left axis deviation, a T-wave inversion in the leads V₁–V₄, and a prolonged QT interval (QTc = 480 ms). Echocardiography revealed a right ventricle-to-left ventricle (RV/LV) ratio of 1.05 with moderate systolic dysfunction and a mildly elevated systolic pulmonary artery pressure (41 mm Hg). Doppler venous ultrasound demonstrated extensive acute iliofemoral deep venous thrombosis. The levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and cardiac troponin I were 0.38 ng/dL and 1160 ng/mL, respectively. PE was confirmed by computed tomography (CT) pulmonary angiography (Figure 1a).

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Figure 1.

Computed tomography pulmonary angiography shows a filling defect (saddle thrombus) (arrow) at the bifurcation of the main pulmonary artery with extension to the main right and left pulmonary artery branches in the first (a) and second (b) patients.

Based on hemodynamic instability and according to the recent European society of cardiology (ESC) recommendation, ⁷ the patient was categorized as high risk PE for which reperfusion therapy was mandatory. ⁷ The patient underwent CDT, which is the main reperfusion strategy in our center. CDT was performed in accordance with our center’s protocol for bilateral PE involvement. First, 2 femoral vein accesses (preferably unilateral) were obtained, and right atrial pressure, pulmonary artery pressure, and pulmonary artery O2 saturation were measured. Thereafter, 2 infusion catheters (Cragg–McNamara Valved Infusion Catheters, Medtronic, Plymouth, MN) were placed in both left and right pulmonary arteries, and 24 mg of tissue plasminogen activator (tPA) (Actilyse, Boehringer Ingelheim, Germany) was infused during a 24-hour period. He developed hematemesis 22 hours after the infusion. Importantly, he had complained of a retrosternal chest pains at least 3 hours of emesis, which no specific management was undertaken by the treating physician. Immediately after clear signs of upper gastrointestinal bleeding (UGIB), the thrombolytic agent and the parenteral anticoagulant were stopped, a nasogastric tube for GI washing was inserted, and intravenous proton pump inhibitors were started. Blood transfusion and intravenous fluid therapy were also started according to GI consult. UGI endoscopy was straightaway scheduled for the patient, and it showed massive submucosal hematoma with oozing (Figure 2a). IHE was confirmed by thoracic spiral CT scanning (Figure 3a and b). Due to the temporary cessation of anticoagulation therapy and the critical condition of our patient, an inferior vena cava (IVC) filter was placed. We followed him with chest CT scanning and found hematoma healing and absorption after a period of 7 days (Figure 3c and d). Fortunately, the patient was stable in terms of PE during the whole period. After 14 days, oral anticoagulation (apixaban) was started and the IVC filters were removed. He was discharged after complete recovery.

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Figure 2.

Upper gastrointestinal endoscopy of the first (a) and second (b) patients shows a massive submucosal hematoma with oozing from the mucosa.

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Figure 3.

Axial (a) and sagittal (b) views of an intramural hematoma detected in the wall of the esophagus in the index thorax computed tomography scan. After a 14-day follow-up, mild thickening of the esophageal wall, along with the resolution of the hematoma, is noted (c and d).

Case 2

The second case was a 62-year-old man, who presented with acute-onset dyspnea of 1 week’s duration. The patient had a history of hypertension and benign prostate hyperplasia, for which he was on tamsulosin, aspirin, and carvedilol. In the emergency department, he had a blood pressure of 83/67 mm Hg, a heart rate of 123 bpm, and O₂ saturation of 91% in the ambient air. Electrocardiography showed sinus tachycardia, a typical S1Q3T3 pattern, and RV strain. Echocardiography demonstrated an RV/LV ratio of 0.98 with moderate systolic dysfunction. The levels of cardiac troponin I and NT-proBNP were 0.45 ng/dL and 3420 ng/mL, correspondingly. PE was confirmed by CT pulmonary angiography (Figure 1b).

Due to the hemodynamic instability, the patient was categorized as high-risk PE, and CDT was proceeded immediately, according to the same protocol applied for the first patient. ⁷ Due to bilateral PE, 2 infusion catheters were placed in both left and right pulmonary arteries, and 24 mg of tPA was infused during a 24-hour period. 18 hours after, hematemesis was occurred. Unfortunately, like the previous case, the second patient had also complained about retrosternal chest pains about 3-4 hours before the UGIB, which was not consider as an important symptom by the treating physician. As previously described for the first patient, fibrinolytic agent was stopped, and GIB workup were proceeded. A massive submucosal hematoma with oozing were detected by UGI endoscopy (Figure 2b) which was confirmed by thoracic spiral CT scan. Anticoagulation therapy has been temporally stopped and due to the risk of re-PE, an inferior vena cava IVC filter were inserted. IHE was absorbed after 10 days in the follow up chest CT scan. According to the GI consult, after 2 weeks, the oral anticoagulation therapy (apixaban) was restarted and IVC filter was removed. The patient was discharge in a good condition.

It should be noted that informed consents have been obtained from both patients for publication of the case report and accompanying images.

Discussion

IHE is a rare condition on the spectrum of esophageal injuries, with the spectrum encompassing the more common Mallory–Weiss tears and Boerhaave’s syndrome. IHE is more commonly seen in middle-aged patients with a small predominance in women. ³ The classical triad comprises chest pain, dysphagia/odynophagia, and hematemesis, which is seen in only about 35% of patients. ⁸ As oral intake in the first few hours after thrombolytic therapy is prohibited, dysphagia and odynophagia might not be detectable in the early stage. Additionally, hematemesis tends to present in the later stages of hematoma. ⁴ Consequently, chest pains might be the only alarming symptoms for a significant length of time. Chest pains are usually sudden-onset, severe, retrosternal, or epigastric pains with radiations to the back. ³ Since chest pains have other important differential diagnoses such as myocardial infarction, aortic dissection, and PE, it is not unlikely for IHE to be overlooked. ⁴ Indeed, both of our patients suffered chest pains 3 to 4 hours before developing hematemesis.

The result of hemorrhage within the esophageal wall, IHE usually involves the submucosal layer and occurs more often in the distal esophagus. Based on the pathogenesis and the nature of the hemorrhage, IHE can be classified into 5 possible categories: 1) abnormal hemostasis, 2) emetogenic, 3) traumatic, 4) spontaneous, and 5) related to aortic disease. ⁹ Spontaneous origin composes one-fifth of the patients. ¹⁰ Spontaneous IHE might occur in the setting of abnormal hemostasis; for instance, thrombolytic and anticoagulation therapy or as a result of pressure fluctuation in the esophagus. ¹⁰ Thrombolytic therapy has been administered for such various clinical scenarios as myocardial infarction, PE, and ischemic stroke. ^2,3,8 Interestingly, in all those cases, thrombolytic agents have been infused at full dose. To our knowledge, the existing literature contains no reports on IHE following CDT. One of the main presumed objectives of CDT is to reduce bleeding complications by decreasing the thrombolytic dosage (approximately one-fourth of the full systemic dose), without affecting the efficacy, via local drug delivery. The occurrence of IHE in the setting of low-dose thrombolytic agents might suggest an idiosyncratic relationship between thrombolytic therapy and IHE.

The diagnosis of IHE can be safely made through several complementary investigations. Plain chest X-ray and cardiac biomarkers have no definitive diagnostic roles but help to exclude other cardiovascular pathologies. Pneumothorax, pneumomediastinum, or pleural effusion might be considered as alarming signs for transmural injuries to the esophagus in the setting of the intramural hematoma. ¹¹ Endoscopy is the initial investigation, especially when hematemesis is the presenting symptom. ³ Endoscopy reveals a bulging, purplish lesion with a smooth and normal overlying mucosa. ³ However, due to the invasive nature of this technique, and the possibility that endoscopy will expand the initial damage, non-contrast CT is now deemed the gold standard diagnostic modality in that it confers a complete evaluation of the esophageal wall and the other mediastinal structures such as the aorta. ² CT typically reveals symmetric or asymmetric esophageal wall thickening with a concentric or eccentric intramural esophageal mass with well-defined borders typically extending along the posterior portion of the esophagus. CT scanning is also useful to determine the presence of complications such as the compression or mass effect on the adjacent airway and the development of infection. ¹²

Once the diagnosis has been established, conservative treatment with, intravenous fluids, withholding the oral intake, antiemetics, and proton pump inhibitors are recommended. ² Bleeding is usually of moderate intensity, and transfusion is necessary in 10% of patients. ¹³ In the initial phase, dietary restriction and serial imaging follow up are of utmost importance. As symptoms improve, oral intake can be started gradually. ¹⁴ IHE is a self-limiting condition, with a generally good prognosis. Indeed, in most cases, the hematoma should resolve within 1 to 3 weeks, with the complete healing of the mucosal tear and the recovery of the normal wall tone and peristalsis. ¹² Endoscopic follow-ups 7 to 14 days afterward have shown ulcers over the involved areas; nonetheless, in most cases, IHE produces no scarring or other sequelae visible at 30 days’ checkups. ¹⁵ However, endoscopy might expose patients to new injuries and, consequently, CT appears to be a safer follow-up modality to ascertain the healing of the esophagus. ¹² Recurrent episodes of bleeding or new odynophagia might point to leakage or rupture and should be immediately investigated. ¹⁴ Surgery for the drainage of the hematoma and the repair of the laceration is rarely needed; still, when necessary, it must be as conservative as possible. ² In complicated cases, a mortality rate of 7% to 9% has been reported with either surgical or medical treatment. ¹⁶

In our patients, we discontinued anticoagulation so as to avert the potential hematoma expansion. We deployed temporary IVC filters for both patients and subsequently removed them after IHE healing. Since both patients have received nearly the total dose of thrombolytic agent (i.e. 24 mg) and the hemodynamic status and clinical condition were stabilized, no further invasive strategies (percutaneous/surgical thrombectomy) were proceeded.

To conclude, we herein described 2 patients complicated by IHE after CDT. Although IHE is a self-limiting condition, with a generally good prognosis following conservative management, it may have devastating consequences. Our experience underscores the importance of regarding IHE as a potential adverse outcome of thrombolytic therapy. Further, our case report shows that thrombolytic-related IHE can occur even with lower doses of thrombolytic agents; thus, we recommend that the physicians who administer low doses of thrombolytic agents for CDT and prosthetic valve thrombosis take heed of the possible occurrence of IHE.